Efforts have been made to determine the etiological agent involved in multiple sclerosis. Several new techniques including direct migration inhibition, lymphocyte cytotoxicity and complement mediated antibody cytotoxicity have been utilized. Cellular immune responses of MS patients and matched controls against measles, rubella, Herpes Simplex virus types I and II, cytomegalovirus were similar. Humoral immune studies confirmed higher measles antibody titers in MS patients than controls. However, other humoral immune tests against rubella, HSV-I and II, and cytomegalovirus indicate that the humoral immune responses of MS patients is not different from that of controls. The role of mycoplasma, and other nonviral agents has been studied. Routine monitoring of cultures from experimental viral studies and efforts to develop new techniques to monitor tissue culture for these nonviral agents have been continued. Efforts to develop a new test for herpesvirus and Varicella Zoster has been successful. We have developed the ELISA technique to measure Varicella Zoster antibody, the use of one dilution of serum in the ELISA technique may make possible rapid determination of antibody levels against Varicella Zoster.